The aim of this review is to discuss the basic science of tumor angiogenesis and recent clinical trial results with angiogenic inhibitors. Colorectal cancer (CRC) continues to be a major cause of all new cancer cases and cancer-related deaths in North America. Although advances in chemotherapy have increased overall survival for patients suffering from metastatic CRC, the survival rate continues to be poor. In order to develop new and more effective therapies for advanced CRC, it is important to understand the basic biologic processes that govern tumor growth. This review will focus on pathways involved in stimulating tumor growth and angiogenesis. Recent excitement has been generated by the clinical efficacy of targeted antiangiogenic therapy against growth factors important in angiogenesis and tumor proliferation. By presenting the basic biology of tumor growth and angiogenesis, we will attempt to explain the therapeutic effects of different angiogenesis inhibitors and speculate how combination treatments with these agents might be beneficial.